The identification of all human genes and their regulatory regions provides the essential framework for our understanding of the molecular basis of disease. There is a lot of enthusiasm for applying next-generation sequencing methods towards achieving the goals of precision medicine. To do so will require us to go beyond genomics and fundamentally understand how genomics impacts on biology and clinical outcomes through gene-gene and gene-environmental interactions. Clinicians and healthcare systems alike need to embrace the cultural and mindset change needed for the implementation of genomics in the clinic.